Aprepitant for the Relief of Nausea in Patients With Chronic Nausea and Vomiting of Presumed Gastric Origin Trial

Aprepitant for the Relief of Nausea in Patients With Chronic Nausea and Vomiting of Presumed Gastric Origin: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Trial

The principal objective of this multicenter, randomized, placebo-controlled trial is to evaluate whether 4 weeks of treatment with aprepitant will improve nausea as compared with placebo in patients with symptoms of chronic nausea and vomiting of presumed gastric origin.

APRON is a multicenter, randomized, double-masked, placebo controlled trial of 4 weeks of treatment with aprepitant or placebo for patients with symptoms of gastroparesis and related disorders. Screening for eligibility and collection of baseline data will span up to 4 weeks after obtaining informed consent and registration. Eligible patients will consist of patients with symptoms of gastroparesis and will be randomized to either aprepitant (125 mg per day) or placebo for 4 weeks.

The symptoms will be measured with the Gastroparesis Cardinal Symptom Index Daily Diary (GCSIDD) for one week at baseline and for four weeks after randomization. In addition, the nausea symptom will be measured daily on a 0 to 100 mm visual analog scale (VAS) for one week at baseline and daily for four weeks after randomization. There will be a 2 week washout period at the end of the treatment to ensure patient safety following the end of treatment.

Inclusion Criteria:

• Age 18 years or older at registration
• Gastric emptying scintigraphy within 2 years of registration
• Normal upper endoscopy or upper GI series within 2 years of registration
• Symptoms of chronic nausea or vomiting compatible with gastroparesis or other functional gastric disorder for at least 6 months (does not have to be contiguous) prior to registration with Gastroparesis Cardinal Symptom Index (GCSI) score of greater than or equal to 21
• Significant nausea defined with a visual analog scale (VAS) score of greater than or equal to 25 mm on a 0 to 100 mm scale

Exclusion Criteria:

• Another active disorder which could explain symptoms in the opinion of the investigator
• Use of narcotics more than 3 days per week
• Significant hepatic injury as defined by significant alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations of greater than 2x the upper limit of normal (ULN) or a Child-Pugh score of 10 or greater
• Contraindications to aprepitant such as hypersensitivity or allergy
• Concurrent use of warfarin, pimozide, terfenadine, astemizole, or cisapride
• Pregnancy or nursing
• Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study
• Failure to give informed consent